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European Journal of Neurology 2008, 15: 885–886
Unraveling depression in ParkinsonÕs disease
Depression is a common psychiatric non-motor symp-
SSRIs sertraline is characterized by a low selectivity
tom occurring in ParkinsonÕs disease (PD) and nega-
for serotonin relative to dopamine reuptake, suggesting
tively aﬀecting patientsÕ quality of life and disability [1].
a favorable eﬃcacy proﬁle. One recent randomized
There is large variability in depression prevalence rates
study showed that sertraline treatment in PD is safe
and this is related to overlap with motor features, dif-
and unlike the tricyclic antidepressant amitriptyline
ﬁculties in the evaluation of cognitively impaired pa-
improves quality of life, particularly activities of daily
tients and lack of scales speciﬁcally designed and
validated for PD. In a prospective study, Hughes et al.
In the current issue of the journal, Kulisevsky
[2] reported that presence of depression and dementia
et al.[12] report the results of 6-month prospective
were important predictors of mortality in PD subjects
evaluation of serterline therapy in a large cohort of 310
followed for over 11 years. In a cohort of 114 PD
depressed PD patients at various disease stages and
patients, Weintraub et al. [3] found that depression and
recruited from over 50 Spanish movement disorder
cognitive impairment were associated with altered
centers. Interestingly, the authors found that sertraline
functional ability, in addition to psychosis, age, PD
treatment not only improved depression but also
duration, apathy, sleepiness, and motor impairment.
resulted in motor beneﬁt as expressed by changes in
Nuti et al. [4] reported in a population of 90 PD sub-
both total Uniﬁed Parkinson’s disease Rating Scale
(UPDRS) and sub-scores including motor. Only a few
according to DSM-IV criteria) were present in 40% of
patients noticed increase of tremor amplitude. The
cases with associated generalized anxiety (11%) and
study is important given the large number of included
panic disorder (30%). Finally, Chaudhuri et al. [5] used
subjects. However, patients were not randomized and
a speciﬁc questionnaire (NMS Quest) to assess non-
neurologists were allowed changes in dopaminergic
motor symptoms and reported that sadness was present
therapy during the observation period making inter-
pretation of the results somehow controversial.
Despite the relevance of depression in PD, there is
Nonetheless, these ﬁndings are complementary to
little evidence for eﬃcacy and safety of antidepressant
those of a randomized study showing that pramipexole,
therapies and trials assessing eﬀectiveness of individual
a dopamine agonist with high aﬃnity for D3 receptors,
drugs are mostly open-label, non-randomized, and
improved both mood and mobility in a cohort of PD
limited to small patient cohorts [6]. A Cochrane review
patients on stable levodopa monotherapy [13].
published in 2003 on the treatment of depression in PD
Some considerations should now be drawn: ﬁrst,
found only three randomized controlled trials on anti-
depression has gained clinical relevance in PD and
depressant medications for a total of 106 patients [7].
application of a revised version of UPDRS along with
The authors concluded that available data on the
speciﬁc questionnaires and scales will help recognition
eﬀectiveness of antidepressant therapies in PD were
of aﬀected patients. Secondly, depression aﬀects quality
insuﬃcient and no recommendation was possible for
of life and patient self-perception of motor function and
this further emphasizes the need for treatment. Thirdly,
This may explain why depression in PD is under-
SSRIs and in particular sertraline have now demon-
treated, at least according to some recent large surveys.
strated good safety and tolerability for clinical use and
The Parkinson Study Group collected data on 23 000
they may be considered ﬁrst line in treating PD
PD patients in the USA and found that 26% was on
depression. Dopamine agonists are also likely to be
treatment with antidepressant drugs [8]. A recent reg-
beneﬁcial and pramipexole is currently evaluated in a
ister-based study in Denmark showed that among
double-blind multicentre study. Finally, eﬀectiveness
22 827 patients on anti-Parkinson medications, 19.9%
and safety should be conﬁrmed in placebo-controlled
were taking antidepressants [9]. Similarly, a cross-sec-
trials. Placebo eﬀect is large in depression and partic-
tional epidemiologic study on non-motor symptoms
ularly in PD. A recent study of rotigotine patch in ad-
conducted in selected movement disorder centers in
vanced PD reported a 35% responder rate to placebo
Italy (PRIAMO) revealed that only 169 of 1072 PD
(vs. 67% to pramipexole and 59.7% to rotigotine) [14].
patients (15.8%) were treated for depression [10].
Therefore, further studies are warranted to ﬁll this
Moreover, serotonin reuptake inhibitors (SSRIs)
important gap, ensure best medical therapy to patients
that are frequently used to treat depression have been
and provide class I evidence of eﬃcacy for anti-
reported to occasionally worsen parkinsonism. Among
Ó 2008 The Author(s)Journal compilation Ó 2008 EFNS
ease. Cochrane database of Systematic Reviews 2003; (3):
Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy
8. Richard IH, Kurlan R and the Parkinson Study Group. A
survey of antidepressant drug use in ParkinsonÕs disease.Neurology 1997; 49: 1168–1170.
9. Brandt-Christensen M, Kvist K, Nilsson FM, Andersen
PK, Kessing LV. Treatment with antiparkinson and
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10. Antonini A, Colosimo C, Marconi R, Morgante L,
Barone P. The PRIAMO study: background, methods
2. Hughes TA, Ross HF, Mindham RH, Spokes EG. Mor-
and recruitment. Neurological Sciences 2008; 29: 61–
tality in ParkinsonÕs disease and its association with
dementia and depression. Acta Neurologica Scandinavica
11. Antonini A, Tesei S, Zecchinelli A, et al. Randomized
study of sertraline and low-dose amitriptyline in patients
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chiatric and other nonmotor symptoms on disability in
of life. Movement Disorders 2006; 21: 1119–1122.
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Gironell A, Garcı´a-Sa´nchez C, Martı´nez-Corral M.
4. Nuti A, Ceravolo R, Piccinni A, et al. Psychiatric com-
Motor changes during sertraline treatment indepressed
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5. Chaudhuri KR, Martinez-Martin P, Schapira AH, et al.
13. Barone P, Scarzella L, Marconi R, et al. Pramipexole
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Journal compilation Ó 2008 EFNS European Journal of Neurology 15, 885–886

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